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The 2016 analysis of 456 pancreatic cancers that grouped 32 recurrently mutated genes into ten pathways and defined four expression subtypes, of which the squamous type has the worst prognosis.
Bailey and colleagues of the Australian Pancreatic Cancer Genome Initiative integrated genomic analysis of 456 pancreatic ductal adenocarcinomas. Thirty-two recurrently mutated genes aggregated into ten pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined four subtypes: squamous (enriched for TP53 and KDM6A mutations, TP63 network upregulation and hypermethylation of pancreatic endodermal cell-fate genes, with poor prognosis), pancreatic progenitor (FOXA2/3, PDX1, MNX1), immunogenic (upregulated immune networks including acquired immune suppression) and aberrantly differentiated endocrine exocrine (ADEX; KRAS activation, exocrine and endocrine differentiation networks). The subtypes correlate with histopathology and, the authors argue, identify opportunities for therapeutic development.
With Moffitt's classical and basal-like split (the squamous and basal-like groups overlap) this fixed the molecular vocabulary of the disease and gave Precision-Panc and the UK's Glasgow group their trial framework.
The classical versus basal-like split, later tied to GATA6 expression and to chemotherapy response, is the subtype scheme most likely to reach the clinic; the stromal subtypes are why the desmoplastic stroma is treated as a partner in the disease rather than inert scar.
The genomic case for platinum in BRCA-type pancreatic cancer, four years before POLO built a maintenance strategy on top of it.
Shares Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma, TGF-β signalling, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Nature, RAS / RAF / MEK / ERK (MAPK), Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares RAS / RAF / MEK / ERK (MAPK), Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Nature, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.